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The Possible Importance of β3 Integrins for Leukemogenesis and Chemoresistance in Acute Myeloid Leukemia

1
Section for Hematology, Department of Medicine, Haukeland University Hospital, N-5021 Bergen, Norway
2
Section for Hematology, Institute of Clinical Science, University of Bergen, 5007 Bergen, Norway
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(1), 251; https://doi.org/10.3390/ijms19010251
Received: 30 November 2017 / Revised: 20 December 2017 / Accepted: 8 January 2018 / Published: 15 January 2018
(This article belongs to the Special Issue Integrins and Human Pathologies)
Acute myeloid leukemia (AML) is an aggressive bone marrow malignancy where the immature leukemia cells communicate with neighboring cells through constitutive cytokine release and through their cell surface adhesion molecules. The primary AML cells express various integrins. These heterodimeric molecules containing an α and a β chain are cell surface molecules that bind extracellular matrix molecules, cell surface molecules and soluble mediators. The β3 integrin (ITGB3) chain can form heterodimers only with the two α chains αIIb and αV. These integrins are among the most promiscuous and bind to a large number of ligands, including extracellular matrix molecules, cell surface molecules and soluble mediators. Recent studies suggest that the two β3 integrins are important for leukemogenesis and chemosensitivity in human AML. Firstly, αIIb and β3 are both important for adhesion of AML cells to vitronectin and fibronectin. Secondly, β3 is important for the development of murine AML and also for the homing and maintenance of the proliferation for xenografted primary human AML cells, and for maintaining a stem cell transcriptional program. These last effects seem to be mediated through Syk kinase. The β3 expression seems to be regulated by HomeboxA9 (HoxA9) and HoxA10, and the increased β3 expression then activates spleen tyrosine kinase (Syk) and thereby contributes to cytokine hypersensitivity and activation of β2 integrins. Finally, high integrin αV/β3 expression is associated with an adverse prognosis in AML and decreased sensitivity to the kinase inhibitor sorafenib; this integrin can also be essential for osteopontin-induced sorafenib resistance in AML. In the present article, we review the experimental and clinical evidence for a role of β3 integrins for leukemogenesis and chemosensitivity in AML. View Full-Text
Keywords: acute myeloid leukemia; integrin; beta3 acute myeloid leukemia; integrin; beta3
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Johansen, S.; Brenner, A.K.; Bartaula-Brevik, S.; Reikvam, H.; Bruserud, Ø. The Possible Importance of β3 Integrins for Leukemogenesis and Chemoresistance in Acute Myeloid Leukemia. Int. J. Mol. Sci. 2018, 19, 251.

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